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Background: Cardiac troponin I (cTnI) has been validated as a sensitive and specific marker of myocyte damage, and is elevated in some patients with congestive heart failure., Objective: To assess the relationship between elevated levels of cTnI and survival in stable patients with congestive heart failure., Patients and Methods: It was assessed whether detectable serial levels of cTnI were associated with mortality in 211 patients with stable, severe heart failure at entry and one month into the Prospective Randomized Flosequinan Longevity Evaluation (PROFILE) study. Of these patients, 66 also had measurements taken at 12 months., Results: Patients were New York Heart Association (NYHA) class III (n=197) or IV (n=14), with a baseline left ventricular ejection fraction of 22+/-7% (range 8% to 35%). Patients with a detectable level of cTnI at one month had an increased mortality (OR 2.608 [95% CI 1.061 to 6.409]; P=0.037). The association between mortality and detectable cTnI levels at baseline or 12 months did not reach statistical significance. Patients with a cTnI level that rose or remained elevated between baseline and one month had a higher mortality rate (50%) than those in whom the cTnI level fell (9%) between baseline and one month (P=0.025). In a multivariate model of survival that included sex, treatment, age, left ventricular ejection fraction, NYHA class and creatinine, only detectable levels of cTnI at one month were associated with survival (P=0.037)., Conclusions: cTnI is released in stable, chronic heart failure and is associated with a poor prognosis, independent of other important risk factors. The risk is particularly elevated when detectable cTnI levels rise or remain elevated over time.

The myocardial contractile protein myosin light chain 1 isoform (MLC-1) is released into the circulation during myocyte necrosis and could thus be a marker of low-grade myocardial damage and of poor prognosis in patients with heart failure. Two hundred eighteen patients with stable heart failure (ejection fraction [EF] <35%) and in New York Heart Association (NYHA) class III to IV had MLC-1 measured at baseline and 1 month after being randomized to the direct vasodilator flosequinan or placebo. Patients were followed a mean of 302 +/- 142 days. The prognostic value of an increase in MLC-1 above the 98th percentile of normal controls was compared with that of conventional prognostic variables in heart failure. MLC-1 was increased in over half of patients at baseline and 1 month, and this was associated with increased age, NYHA class IV, and renal insufficiency. By Kaplan-Meier survival analysis, patients with a baseline increase in MLC-1 had a greater mortality (26%) than those without an increase (15%) (p = 0.043). A significant interaction among MLC-1, survival, and treatment was found (p = 0.043). In the placebo group, MLC-1 was associated with increased mortality (29% vs 12%, p = 0.025), whereas there was no significant difference among patients receiving flosequinan. In a multivariate logistic regression model including age, treatment, and left ventricular (LV) ejection fraction, the MLC-1 chain was most predictive of mortality (p = 0.049). Thus, circulating MLC-1 is elevated in over half of patients with stable severe heart failure, and this increase is associated with a poor prognosis. Flosequinan treatment eliminates this association, highlighting the complexity of the relation between cardiac myocyte damage, drug treatment, and mortality.

Background: Cardiac troponins are reliable markers of myocardial injury that are being used increasingly in patients presenting with undifferentiated chest pain or dyspnea to diagnose an acute coronary syndrome. If elevated cardiac troponin levels also occur in patients with pulmonary embolism because of right ventricular dilation and myocardial injury, such patients could be misdiagnosed. We performed a prospective cohort study to determine the prevalence of elevated cardiac troponin I (cTnI) levels in patients with submassive pulmonary embolism., Methods: Consecutive patients with objectively confirmed submassive pulmonary embolism and no previous history of ischemic heart disease, other cardiac disease, or renal insufficiency were included. Creatine kinase and cTnI levels were measured within 24 hours of clinical presentation on 2 occasions 8 to 12 hours apart., Results: Of 24 patients with submassive pulmonary embolism, 5 (20.8%) had elevated cTnI levels of 0.4 microg/L or higher (95% confidence interval, 7.1-42.2%). One of these patients had a cTnI level higher than 2.3 microg/L that was suggestive of myocardial infarction., Conclusion: Pulmonary embolism should be considered in the differential diagnosis of patients presenting with undifferentiated chest pain or dyspnea and an elevated cardiac troponin level.

Study Objectives: To determine whether lumbar epidural anesthesia, when combined with general anesthesia, decreases perioperative blood loss, the incidence of postoperative deep vein thrombosis (DVT), cardiac dysrhythmias, and ischemia in patients undergoing total hip arthroplasty (THA)., Design: Randomized, controlled study., Setting: A university hospital., Patients: 37 ASA physical status I, II, and III patients, undergoing elective THA., Intervention: Patients were divided into two statistically comparable groups: Group GA = general anesthesia; Group CEGA = general anesthesia plus lumbar epidural anesthesia. All patients had 48-hour perioperative Holter monitoring, applied on admission, the day prior to surgery. In both groups, general anesthesia was induced with thiopental sodium and muscle relaxant, and maintained with oxygen, nitrous oxide, isoflurane, opioid, and muscle relaxant. Group B received lumbar epidural anesthesia with 10 ml 0.5% bupivacaine with 1:200,000 epinephrine prior to anesthesia induction. Blood loss was measured by suction bottle contents, sponge weights, and collection drainage. DVT was assessed with postoperative leg scanning, plethysmography, and venogram., Measurements and Main Results: Intraoperative blood loss was less after combined epidural-general anesthesia (663.8 ml +/- 299.0 ml) than after general anesthesia alone (1,259.2 ml +/- 366.0 ml). The difference was found to be statistically significant (p < 0.00005). No difference was found between the two groups in postoperative blood loss, incidence of DVT, cardiac dysrhythmias, or ischemia., Conclusion: Combined regional-general anesthesia decreases intraoperative blood loss in THA, and thereby offers an advantage over general anesthesia alone.

Background: Dipyridamole imaging is widely used as an alternative to exercise testing to identify and risk stratify patients with coronary artery disease. Safety data on intravenous dipyridamole stress testing has been derived largely from individual institutional data., Methods and Results: Data were collected retrospectively by 85 coinvestigators from 73,806 patients who underwent intravenous dipyridamole stress imaging in 59 hospitals and 19 countries to determine the incidence of major adverse reactions during testing. The dose of dipyridamole infused was 0.56 mg/kg in 64,740 patients, 0.74 mg/kg in 6551 patients, and 0.84 mg/kg in 2515 patients. Combined major adverse events among the entire 73,806 patients included seven cardiac deaths (0.95 per 10,000), 13 nonfatal myocardial infarctions (1.76 per 10,000), six nonfatal sustained ventricular arrhythmias (0.81 per 10,000) (ventricular tachycardia in two and ventricular fibrillation in four), nine transient cerebral ischemic attacks (1.22 per 10,000), (with speech or motor deficit), one stroke, and nine severe bronchospasms (1.22 per 10,000) (one intubation and eight near intubations). In addition to the safety data, detailed demographic, peripheral hemodynamic, side effect, and concomitant drug data were examined in a subgroup of 3751 patients. End points from subsets of patients were compared with those of the group as a whole. Multivariate analysis revealed that dipyridamole-induced chest pain was more common in patients less than 70 years old (p = 0.0017), those with a history of coronary revascularization (p = 0.002), or patients taking aspirin (p = 0.0001). Minor noncardiac side effects were less frequent among the elderly (p = 0.0053) and more frequent in women (p = 0.0001) and patients taking maintenance aspirin (p = 0.0034). When a patient was judged on the basis of the adequacy of hemodynamic response to be a dipyridamole "nonresponder" (< 10 mm Hg drop in systolic blood pressure and 10 beats/min increase in heart rate), the only significant predictor was angiotensin-converting enzyme inhibitor intake (p = 0.0025). Inferoposterior hypoperfusion was significantly more frequent in patients with dipyridamole-induced hypotension: 57% (44/77) (p < 0.0001) of those who had hypotension and 89% (8/9) (p = 0.0076) who had severe symptomatic bradyarrhythmias displayed inferoposterior defects on thallium scanning. Caffeine levels were determined in 391 consecutive patients: levels greater than 5 mg/L were observed in only eight patients (2%), suggesting that methylxanthine levels sufficient to alter the hemodynamic response to dipyridamole resulting in suboptimal hyperemic stress are unlikely when patients take nothing by mouth after midnight., Conclusion: The risk of serious dipyridamole-induced side effects is very low and is comparable to that reported for exercise testing in a similar patient population.